Associating Site Characteristics With Distributions of Pestiferous and Predaceous Arthropods in Soybean.
Although site-specific pest management has the potential to decrease control costs and environmental impact associated with traditional pest management tactics, the success of these programs relies on the accurate characterization of arthropod distributions within a crop. Because potential correlation of insect counts with remotely sensed field attribute data could help to decrease the costs associated with and need for fine-scale spatial sampling, we chose to determine which within-field variables would be informative of soybean arthropod counts in an attempt to move toward site-specific pest management in this crop. Two soybean fields were grid-sampled for pestiferous and predaceous arthropods, plant productivity estimates, and abiotic variable characterization in 2017-2018. Negative binomial, zero-inflated models were used to estimate presence and counts of soybean arthropod taxa based on normalized difference vegetation index (NDVI), soybean plant height, soil electrical conductivity (ECa), elevation, and calendar week. Among all variables, calendar week was the most reliable predictor of arthropod counts, as it was a significant predictor for a majority of all taxa. Additionally, counts for a majority of pestiferous taxa were significantly associated with distance from the field edge, elevation, soybean plant height, and NDVI. Although site-specific pest management has the potential for reduced management inputs and increased profitability over conventional management (i.e., whole-field) practices, management zones must first be clearly defined based on the within-field variability for the variables of interest. If site-specific pest management practices are to be applied in soybean, calendar week (and associated soybean phenology), soybean plant height (and associated elevation), and NDVI may be useful for describing the distributions of pests, such as kudzu bug, Megacopta cribraria (Hemiptera: Plataspidae) (Fabricius), green cloverworm, Hypena scabra (Lepidoptera: Erebidae) (Fabricius), velvetbean caterpillar, Anticarsia gemmatalis (Lepidoptera: Erebidae) (Hübner), and soybean looper, Chrysodeixis includens (Lepidoptera: Noctuidae) (Walker).


Ino2, activator of yeast phospholipid biosynthetic genes, interacts with basal transcription factors TFIIA and Bdf1.
Binding of general transcription factors TFIID and TFIIA to basal promoters is rate-limiting for transcriptional initiation of eukaryotic protein-coding genes. Consequently, activator proteins interacting with subunits of TFIID and/or TFIIA can drastically increase the rate of initiation events. Yeast transcriptional activator Ino2 interacts with several Taf subunits of TFIID, among them the multifunctional Taf1 protein. In contrast to mammalian Taf1, yeast Taf1 lacks bromodomains which are instead encoded by separate proteins Bdf1 and Bdf2. In this work, we show that Bdf1 not only binds to acetylated histone H4 but can also be recruited by Ino2 and unrelated activators such as Gal4, Rap1, Leu3 and Flo8. An activator-binding domain was mapped in the N-terminus of Bdf1. Subunits Toa1 and Toa2 of yeast TFIIA directly contact sequences of basal promoters and TFIID subunit TBP but may also mediate the influence of activators. Indeed, Ino2 efficiently binds to two separate structural domains of Toa1, specifically with its N-terminal four-helix bundle structure required for dimerization with Toa2 and its C-terminal β-barrel domain contacting TBP and sequences of the TATA element. These findings complete the functional analysis of yeast general transcription factors Bdf1 and Toa1 and identify them as targets of activator proteins.


Central blood pressure: current evidence and clinical importance.
Pressure measured with a cuff and sphygmomanometer in the brachial artery is accepted as an important predictor of future cardiovascular risk. However, systolic pressure varies throughout the arterial tree, such that aortic (central) systolic pressure is actually lower than corresponding brachial values, although this difference is highly variable between individuals. Emerging evidence now suggests that central pressure is better related to future cardiovascular events than is brachial pressure. Moreover, anti-hypertensive drugs can exert differential effects on brachial and central pressure. Therefore, basing treatment decisions on central, rather than brachial pressure, is likely to have important implications for the future diagnosis and management of hypertension. Such a paradigm shift will, however, require further, direct evidence that selectively targeting central pressure, brings added benefit, over and above that already provided by brachial artery pressure.


Suilloid fungi as global drivers of pine invasions.
Belowground biota can deeply influence plant invasion. The presence of appropriate soil mutualists can act as a driver to enable plants to colonize new ranges. We reviewed the species of ectomycorrhizal fungi (EMF) that facilitate pine establishment in both native and non-native ranges, and that are associated with their invasion into nonforest settings. We found that one particular group of EMF, suilloid fungi, uniquely drive pine invasion in the absence of other EMF. Although the association with other EMF is variable, suilloid EMF are always associated with invasive pines, particularly at early invasion, when invasive trees are most vulnerable. We identified five main ecological traits of suilloid fungi that may explain their key role at pine invasions: their long-distance dispersal capacity, the establishment of positive biotic interactions with mammals, their capacity to generate a resistant spore bank, their rapid colonization of roots and their long-distance exploration type. These results suggest that the identity of mycorrhizal fungi and their ecological interactions, rather than simply the presence of compatible fungi, are key to the understanding of plant invasion processes and their success or failure. Particularly for pines, their specific association with suilloid fungi determines their invasion success in previously uninvaded ecosystems.


Alteration of benzo(a)pyrene metabolism by acute ethanol or corticosterone.
The effect of acute ethanol (3 g/kg and 5 g/kg) or corticosterone (12.5 mg/kg) on benzo(a)pyrene metabolism was measured in microsomes from 3-methylcholanthrene pretreated rats. BAP disappearance was inhibited 34% at 5 g/kg but unaltered at 3 g/kg ethanol. Corticosterone administration inhibited BAP metabolism 53%. In adrenalectomized (ADX) rats, alcohol or CS did not decrease BAP metabolism (compared to untreated ADX rats). However, corticosterone in vitro inhibited BAP metabolism in a dose-related fashion in washed microsomes from untreated rats. These results demonstrate that acute ethanol and corticosterone administration alter benzo(a)pyrene metabolism. Furthermore, the inhibition requires an intact adrenal.


Stereoselective behavioral effects of the isomers of pentobarbital and secobarbital in the pigeon.
Little information is available on the contribution of the isomers of pentobarbital and secobarbital to the behavioral effects of the racemic mixtures. To determine the contribution of each isomer on food-maintained behavior, pigeons were trained to respond under either a multiple fixed-ratio 30, fixed-interval 600 (mult FR30 FI600) schedule, or a multiple fixed-ratio 30, variable-interval 60-sec (mult FR30 VI60) schedule under which every response under both the FR and VI components also produced a brief electrical shock (punishment). Dose-response curves were determined separately for each isomer of pentobarbital (1-17.5 mg/kg i.m.) and secobarbital (1-17.5 mg/kg i.m.). Under the mult FR30 FI600 schedule, the S-(-)-isomers of pentobarbital and secobarbital were slightly less than 2-fold more potent than the R-(+)-isomers, but both isomers produced qualitatively similar effects on responding. The S-(-)-isomers of both barbiturates produced increases in punished responding under the mult FR30 VI60 at lower doses than the R-(+)-isomers. At high doses (greater than 10 mg/kg), the S-(-)-isomers suppressed responding early in the session resulting in a lower average rate of punished responding for the session than the R-(+)-isomers. The peak increase in punished responding was observed after 10 mg/kg of the R-(+)-isomers of pentobarbital and secobarbital. These results indicate that the effect of the isomers of pentobarbital and secobarbital on mult FR30 FI600 responding and on suppressed responding are qualitatively similar.(ABSTRACT TRUNCATED AT 250 WORDS)


A conceptual framework for the domain of evidence-based design.
The physical facilities in which healthcare services are performed play an important role in the healing process. Evidence-based design in healthcare is a developing field of study that holds great promise for benefiting key stakeholders: patients, families, physicians, and nurses, as well as other healthcare staff and organizations. In this paper, the authors present and discuss a conceptual framework intended to capture the current domain of evidence-based design in healthcare. In this framework, the built environment is represented by nine design variable categories: audio environment, visual environment, safety enhancement, wayfinding system, sustainability, patient room, family support spaces, staff support spaces, and physician support spaces. Furthermore, a series of matrices is presented that indicates knowledge gaps concerning the relationship between specific healthcare facility design variable categories and participant and organizational outcomes. From this analysis, the authors identify fertile research opportunities from the perspectives of key stakeholders.


Molecular characterization of the transition to malignancy in a genetically engineered mouse-based model of ductal carcinoma in situ.
A transplantable model of human ductal carcinoma in situ that progresses to invasive carcinoma was developed from a genetically engineered mouse (GEM). Additional lines were established using early mammary premalignant lesions from transgenic MMTV-PyV-mT mice. These lines were verified to be premalignant and transplanted repeatedly to establish stable and predictable properties. Here, we report the first in-depth molecular analysis of neoplastic progression occurring in one premalignant transplantable GEM-derived line. Oligonucleotide microarrays showed that many genes are differentially expressed between the quiescent and prelactating mammary gland and the premalignant GEM outgrowth. In contrast, a small but consistent group of genes was associated with the transformation from premalignancy to tumor. This suggests that the majority of gene expression changes occur during the premalignant transition from normal to premalignancy, whereas many fewer changes occur during the malignant transition from premalignancy to invasive carcinoma. The premalignant transition is associated with several cell cycle-related genes and the up-regulation of oncogenes is associated with various cancers (Ccnd11, Cdk4, Myb, and Ect2). The changes identified in the malignant transition included genes previously associated with human breast cancer progression. Misregulation of the insulin-like growth factor and transforming growth factor-beta signaling pathways and the stromal-epithelial interaction were implicated. Our results suggest that this transplantable GEM-based model recapitulates human ductal carcinoma in situ at both histologic and molecular levels. With consistent tumor latency and molecular profiles, this model provides an experimental platform that can be used to assess functional genomics and molecular pharmacology and to test promising chemoprevention strategies.


Psychometric analysis of the Brisbane Practice Environment Measure (B-PEM).
To undertake rigorous psychometric testing of the newly developed contemporary work environment measure (the Brisbane Practice Environment Measure [B-PEM]) using exploratory factor analysis and confirmatory factor analysis. Content validity of the 33-item measure was established by a panel of experts. Initial testing involved 195 nursing staff using principal component factor analysis with varimax rotation (orthogonal) and Cronbach's alpha coefficients. Confirmatory factor analysis was conducted using data from a further 983 nursing staff. Principal component factor analysis yielded a four-factor solution with eigenvalues greater than 1 that explained 52.53% of the variance. These factors were then verified using confirmatory factor analysis. Goodness-of-fit indices showed an acceptable fit overall with the full model, explaining 21% to 73% of the variance. Deletion of items took place throughout the evolution of the instrument, resulting in a 26-item, four-factor measure called the Brisbane Practice Environment Measure-Tested. The B-PEM has undergone rigorous psychometric testing, providing evidence of internal consistency and goodness-of-fit indices within acceptable ranges. The measure can be utilised as a subscale or total score reflective of a contemporary nursing work environment. An up-to-date instrument to measure practice environment may be useful for nursing leaders to monitor the workplace and to assist in identifying areas for improvement, facilitating greater job satisfaction and retention.


Responses to odors mapped in snail tentacle and brain by [14C]-2-deoxyglucose autoradiography.
The method of 2-deoxyglucose (2-DG) autoradiography has been widely used to map functional neuronal systems in vertebrates, but in invertebrate species, where morphological dimensions favor its use, the applications have been minimal. This study uses [14C]-2-DG to map the olfactory system of a terrestrial snail, Achatina fulica. The olfactory organ in the snail's tentacles bears a striking resemblance to the vertebrate olfactory mucosa. There are also complex neural structures in the tentacle and brain that are devoted to subsequent processing. These facts make the molluscan olfactory system a suitable complement to the traditional vertebrate and insect models in olfaction. The experiments utilized intact snails in which one tentacle was exposed to a controlled odor environment while the contralateral tentacle was held in a retracted position. The dose of [14C]-2-DG (2 microCi/gm) was injected into the hemocele. Tissue processing involved freeze-substitution with acetone, dry sectioning, and the preparation of liquid film autoradiographs. Optical density measurements permitted quantitative comparisons between experimental conditions. The natural odors of conspecific snails and of carrots elicited significantly more uptake of 2-DG in the exposed tentacle than in the unexposed tentacle and, in the exposed tentacle, significantly more label over the axons of the primary sensory neurons than was elicited by exposure to clean air. Amyl acetate and octanol were less effective. A small number of superficially placed sensory neurons were labeled in all stimulus conditions, including clean air, and may represent the mechanosensors. Stimulus-dependent labeling in the brain was limited to the procerebrum and included both neuropilar and cellular parts. In contrast to vertebrate and insect olfactory systems, there was no evidence of spatial coding for odor quality.


Effects of intravenous anesthetic agents on pregnant myometrium.
Emergent or elective surgical procedures under general anesthesia may be required during pregnancy for some patients. For this reason, effects of anesthetics on uterine contractions are important. General anesthesia is not limited to the administration of inhalation agents, since induction and maintenance of anesthesia usually involve intravenous administration of different anesthetic agents. The effects of these agents on uterine contractions and blood flow are very important. The unexpected relaxation or contraction of myometrium can be harmful to fetus and continuing pregnancy. Our aim in this study is to investigate the effects of intravenous anesthetic agents on uterine contractions. In our study, we examined the effects of ketamine, propofol and midazolam on contractions of isolated pregnant rat myometrium. We observed that exposure to propofol, ketamine and midazolam at the concentrations of 10(-5)-10(-4) M decreased spontaneous contractile activity in myometrial strips isolated from pregnant rats. There was statistically significant difference between the control and all strips exposed to propofol, ketamine and midazolam in the contraction amplitude and integrated area under the contraction curve.


[Lungtransplantation in Sweden - over 1 200 patients transplanted since 1990].
Lung transplantation is an accepted treatment for end stage lung diseases and performed at two national centers in Sweden - Gothenburg and Lund. Since the start in 1990 over 1 200 patients have been transplanted. The indications are severe progressive lung diseases with short expected survival or severe negative effects on daily life. There are several contraindications among which severe other organ disease, recent malignancy or psychiatric disease are most important. The most common causes for lung transplantation are chronic obstructive pulmonary disease (COPD), interstitial pulmonary disease, cystic fibrosis and pulmonary hypertension. Long term survival after 5 years is 63 %, and after 10 years 48 %, which is better than the results reported in the international registry (57 % and 36 % respectively). Lung transplantation is today a therapy for end stage pulmonary diseases with acceptable survival results. It is likely that the number of patients will increase in the future.


A comparative kinematic analysis of cyclical bending in patients with early stages of Parkinson's disease and in patients with essential tremor.
Early stage Parkinson's disease (PD) shares certain symptoms with essential tremor (ET), which makes it difficult to differentiate between the two. We analyzed cyclical body bends to find kinematic parameters that are capable of differentiating among PD, ET and normal control (NC) subjects. A linear discriminant analysis of the joint angles showed a reliable distinction between NC and the two groups of patients, while differentiating reasonably well between PD and ET. PD patients showed difficulty performing hip segment rotation around the vertical axis, whereas ET patients demonstrated enlarged torso sway in the frontal plane. These findings suggest that kinematic parameters of body movement in the standing position are sensitive enough to serve as subclinical marks in the early diagnosis of PD and ET.


[Congenital Chagas disease in Geneva: diagnostic and clinical aspects].
Chagas disease, a parasitic infection with Trypanosoma cruzi, recently emerged in Europe and in Switzerland. Mother-to-child infection represents a major mode of transmission in non endemic areas. In 2008, 305 Latin American pregnant women consulting at the Geneva University Hospitals were screened by serology. Overall prevalence was 2% and 8.8% in Bolivian women. All infected women were in the indeterminate form of the chronic phase. Two newborns were congenitally infected. Considering the potential for vertical transmission and the risk of long-term complications, screening programs for persons at risk need to be implemented.


Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel (DERBI study).
To evaluate the outcome of second-line intravitreal ranibizumab treatment in eyes with diabetic macular edema having persistent edema following initial therapy with intravitreal bevacizumab. Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel was a retrospective, multi-center study. Consecutive eyes with persistent diabetic macular edema following at least three previous intravitreal bevacizumab injections prior to intravitreal ranibizumab, at least three-monthly intravitreal ranibizumab injections and at least 12 months of follow-up were included. Data collected included demographics, ocular findings, diabetes control, details of intravitreal bevacizumab and ranibizumab injections, and visual and anatomical measurements before and after intravitreal ranibizumab treatment. In total, 202 eyes of 162 patients treated at 11 medical centers across Israel were included. Patients received a mean (±standard deviation) of 8.8 ± 4.9 intravitreal bevacizumab injections prior to the switch to intravitreal ranibizumab. A mean of 7.0 ± 2.7 intravitreal ranibizumab injections were given during the 12 months following the switch to intravitreal ranibizumab. The median central subfield retinal thickness (±interquartile range) by spectral-domain optical coherence tomography decreased from 436 ± 162 µm at baseline to 319 ± 113 µm at month 12 (p < 0.001). Median logMAR visual acuity (±interquartile range) improved from 0.40 ± 0.48 at baseline to 0.38 ± 0.40 at month 12 (p = 0.001). Linear regression suggested that higher number of intravitreal ranibizumab injections and higher pre-switch central subfield retinal thickness were associated with favorable visual outcome. Higher number of intravitreal bevacizumab injections and the presence of intraretinal fluid before the switch lessened the odds of favorable outcome. Switching from bevacizumab to ranibizumab in persistent diabetic macular edema was associated with anatomical improvement in the majority of eyes and ⩾2 lines of vision improvement in 22% of eyes.


ON direction-selective ganglion cells in the rabbit retina: dendritic morphology and pattern of fasciculation.
ON direction-selective (DS) ganglion cells were identified by electrophysiological recordings in DAPI labeled, isolated rabbit retinas. Their responses to a flashing spot were sustained. Their responses to moving stimuli were strong in the preferred direction and weak in the null direction. Injection of the recorded cells with Lucifer yellow revealed that the cells had a distinct dendritic morphology, consistent with that described previously (Buhl & Peichl, 1986; Amthor et al., 1989; Famiglietti, 1992a). When neighboring cells were injected, an extensive dendritic co-fasciculation was observed. The pattern of fasciculation restricts the possible synaptic connections of the ON DS cell.


Differential regulation of neurogenesis by the two Xenopus GATA-1 genes.
Previously, we have shown that the ventralizing factor bone morphogenetic protein 4 (BMP-4) can inhibit Xenopus neurogenesis. The erythroid transcription factor GATA-1 functions downstream of the BMP-4 signaling pathway and mediates BMP-4-induced erythropoiesis. We have found that similar to BMP-4, GATA-1b inhibits neuralization of Xenopus animal cap (AC) cells. The neural inhibition is not seen with GATA-1a, although both GATA-1a and GATA-1b RNAs are translated at the same efficiency and induce globin expression equally in AC cells. GATA-1b RNA injection into AC cells neither induces expression of Xbra (a general mesoderm marker) nor affects expression of XK81 (epidermal keratin) or BMP-4 and Xvent-1 (two ventral markers). These data suggest that GATA-1b retains the epidermal fate of the AC. Intact GATA-1b protein is required for both inhibition of neurogenesis and induction of globin expression. Our findings indicate that GATA-1b can function in ectoderm to specifically regulate neural inducing mechanisms, apparently related to the expression of chordin, a neuralizing gene. Furthermore, tadpole stage embryos injected with GATA-1b are devoid of all dorsoanterior structures including neural tissue. This report provides evidence that the two transcription factors, derived from a recent genome duplication, share a common biological activity (stimulation of erythropoiesis) while also exhibiting a distinct function (inhibition of neurogenesis).


Blackberry juice anthocyanidins limit cisplatin-induced renal pathophysiology in mice.
Some studies have showed that intake of blackberry juice (BBJ) can prevent urinary tract infections. However, there is a lack of studies that evaluate the mechanisms by which BBJ has protective effect. Thus, the aim of current study was to evaluate the effects of BBJ supplementation on cisplatin-induced renal pathophysiology in mice. Mice were supplemented with BBJ (10 mL/kg) for seven days. One hour after the last supplementation with BBJ, mice received cisplatin (10 mg/kg, i.p.). Seventy-two hours after cisplatin administration, blood was collected and biochemical analysis were performed (urea and creatinine), kidney was dissected and utilized in histological and oxidative evaluations. Cisplatin caused severe injury in renal tissue, in markers of renal damage (urea and creatinine) generated increased of plasmatic levels. Besides that, the cisplatin induced decreased of enzymes activities in renal tissue (superoxide dismutase, glutathione S-transferase and catalase). In contrast, BBJ supplementation protected against histopathological alterations through decreased in urea and creatinine levels and modulation of catalase enzyme activity. Thus, BBJ supplementation protected the renal system of mice from deleterious effects. We suggest that high concentrations of Cyanidin 3-O-glucoside and Cyanidin 3-O-rutinoside are responsible for antioxidant role of BBJ supplementation in renal pathophysiology induced by cisplatin exposure. Also, these results reinforcing the importance of including BBJ in the human diet aimed at preventing renal diseases.


Cultivation of cereals by the first farmers was not more productive than foraging.
Did foragers become farmers because cultivation of crops was simply a better way to make a living? If so, what is arguably the greatest ever revolution in human livelihoods is readily explained. To answer the question, I estimate the caloric returns per hour of labor devoted to foraging wild species and cultivating the cereals exploited by the first farmers, using data on foragers and land-abundant hand-tool farmers in the ethnographic and historical record, as well as archaeological evidence. A convincing answer must account not only for the work of foraging and cultivation but also for storage, processing, and other indirect labor, and for the costs associated with the delayed nature of agricultural production and the greater exposure to risk of those whose livelihoods depended on a few cultivars rather than a larger number of wild species. Notwithstanding the considerable uncertainty to which these estimates inevitably are subject, the evidence is inconsistent with the hypothesis that the productivity of the first farmers exceeded that of early Holocene foragers. Social and demographic aspects of farming, rather than its productivity, may have been essential to its emergence and spread. Prominent among these aspects may have been the contribution of farming to population growth and to military prowess, both promoting the spread of farming as a livelihood.


T cell subpopulation in hepatoma.
The determination of T cell subpopulation is a modern development in immunology. The increase or hyperactivity of suppressor T cells plays an important role in the development of immune deficiency diseases and most tumors. Our 15 cases of hepatoma, which have all been confirmed with clinical and pathological evidence, belong to the rapid-growing type. Suppressor (Tr) cell elevation appears in the early stage; and the more severe and late the disease is, the higher the Tr cell increase. Thus, the determination of T cell subpopulations bears a close relationship to the evaluation of early hepatoma and to the prognosis of the disease.


Anti-inflammatory potential of chia seeds oil and mucilage against adjuvant-induced arthritis in obese and non-obese rats.
Background Natural anti-inflammatory nutraceuticals may be useful in suppressing the incessant aggravation of rheumatoid arthritis. Chia seeds as a natural source of antioxidants help prevent several oxidative stress-mediated diseases. The current study was focused on arthritis combined with obesity and evaluated the validation of oil and mucilage extracted from chia seeds as anti-inflammatory nutraceuticals in obese and non-obese adjuvant arthritic rat model. Methods Chia seeds oil was extracted by pressing method, whereas the mucilage was extracted using water (50 °C for 30 min). Oil and freeze-dried mucilage were tested for their anti-inflammatory effects using 48 male Sprague-Dawley rats. Obesity was developed in rats after 8 weeks of feeding on high-fat high-sucrose diet; on the first day of the ninth week, chia seeds oil and mucilage were administrated for 21 days, and arthritis was induced either in obese or non-obese rats via the injection with Freund's complete adjuvant. Swelling of the paw was then measured. Plasma tumor necrosis factor (TNF-α), lipid profile, liver and kidney functions, serum lipid peroxidation, and erythrocyte catalase activity were determined. Results Results emphasized that arthritis with obesity resulted in the elevation of the swelling of the paw, TNF-α, dyslipidemia, and oxidative stress. Chia seeds oil and mucilage, more promisingly the oil, attenuated TNF-α and the swelling of the paw, improved lipid profile, and diminished the oxidative stress both in obese and non-obese arthritic rats. Conclusions Results showed that chia seeds oil and mucilage exhibited anti-inflammatory effects against adjuvant-induced arthritis in obese and non-obese rats.


Impact of automatic acquisition of key clinical information on the accuracy of electrocardiogram interpretation: a cross-sectional study.
The accuracy of electrocardiogram (ECG) interpretation by doctors are affected by the available clinical information. However, having a complete set of clinical details before making a diagnosis is very difficult in the clinical setting especially in the early stages of the admission process. Therefore, we developed an artificial intelligence-assisted ECG diagnostic system (AI-ECG) using natural language processing to provide screened key clinical information during ECG interpretation. Doctors with varying levels of training were asked to make diagnoses from 50 ECGs using a common ECG diagnosis system that does not contain clinical information. After a two-week-blanking period, the same set of ECGs was reinterpreted by the same doctors with AI-ECG containing clinical information. Two cardiologists independently provided diagnostic criteria for 50 ECGs, and discrepancies were resolved by consensus or, if necessary, by a third cardiologist. The accuracy of ECG interpretation was assessed, with each response scored as correct/partially correct = 1 or incorrect = 0. The mean accuracy of ECG interpretation was 30.2% and 36.2% with the common ECG system and AI-ECG system, respectively. Compared to the unaided ECG system, the accuracy of interpretation was significantly improved with the AI-ECG system (P for paired t-test = 0.002). For senior doctors, no improvement was found in ECG interpretation accuracy, while an AI-ECG system was associated with 27% higher mean scores (24.3 ± 9.4% vs. 30.9 ± 10.6%, P = 0.005) for junior doctors. Intelligently screened key clinical information could improve the accuracy of ECG interpretation by doctors, especially for junior doctors.


Is chromosome in situ suppression (CISS) hybridization suited as a predictive test for intrinsic radiosensitivity in cancer patients?
Chromosome painting (chromosome in situ suppression hybridization, CISS) analyses were used to control in vitro radiosensitivity of peripheral blood lymphocytes of 70 cancer patients who were assigned to or had just undergone radiation therapy. This technique using three-colour detection of genomic DNA libraries of chromosomes 1, 2, and 4 was shown to uncover reliably radiation-induced chromosome damage in human peripheral blood lymphocytes. The lymphocytes of five out of the 70 cancer patients could be defined as to react hypersensitively to in vitro irradiation. This was particularly underlined not only by the mere increase of aberration rate but also by the quality of the induced abnormalities (e.g. incidence of complex chromosome rearrangements). The same patients were also characterized by extreme radiation reaction in clinical terms. In spite of some confounding factors, based on the presented observations, the CISS-technique can be proposed as a predictive technique for selecting radiosensitive patients and protecting them from undesired side effects of radiotherapy. A simplification of the screening procedure is proposed on the basis of the presented data.


[Epidemiology, resource use and costs of rheumatoid arthritis in Argentina].
This review aims to identify information on epidemiological parameters and estimate the cost of moderate to severe rheumatoid arthritis (RA). A search for related literature was carried out in major databases. A consensus of local rheumatology experts was used to find the most realistic parameters, using a modified Delphi method. Direct medical costs were estimated, using information collected from the cost per unit database of the Instituto de Efectividad Clínica y Sanitaria de Argentina. Indirect costs were estimated using the human resources approach. Costs were expressed in US dollars (USD) as of November 2017. The reported prevalence of RA in Argentina was 0.94% (95%CI: 0.86 to 1.02), with an annual incidence rate of 19 per 100,000 people (95%CI: 17 to 20). The annual cost of disease-modifying drugs was 33,936.10 USD per patient. The cost attributed to serious infections was 2,474.6 USD. The cost of bilateral knee replacement per patient was $5,276.8 USD; and the cost for total hip replacement was $9,196.4. Both, the cost of hospitalization days per patient per year, and the indirect costs of RA increased as the disability score increased. This review reports useful information on epidemiological and cost parameters of moderate to severe RA, in the era of biological agents, in order to be useful for conducting economic evaluations regarding health in Argentina.


Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide.
Hydrogen sulphide (H(2)S) is an endogenous gaseous signaling molecule and potential therapeutic agent. Emerging studies indicate its therapeutic potential in a variety of cardiovascular diseases and in critical illness. Augmentation of endogenous sulphide concentrations by intravenous administration of sodium sulphide can be used for the delivery of H(2)S to the tissues. In the current study, we have measured H(2)S concentrations in the exhaled breath of healthy human volunteers subjected to increasing doses sodium sulphide in a human phase I safety and tolerability study. We have measured reactive sulphide in the blood via ex vivo derivatization of sulphide with monobromobimane to form sulphide-dibimane and blood concentrations of thiosulfate (major oxidative metabolite of sulphide) via ion chromatography. We have measured exhaled H(2)S concentrations using a custom-made device based on a sulphide gas detector (Interscan). Administration of IK-1001, a parenteral formulation of Na(2)S (0.005-0.20 mg kg(-1), i.v., infused over 1 min) induced an elevation of blood sulphide and thiosulfate concentrations over baseline, which was observed within the first 1-5 min following administration of IK-1001 at 0.10 mg kg(-1) dose and higher. In all subjects, basal exhaled H(2)S was observed to be higher than the ambient concentration of H(2)S gas in room air, indicative of on-going endogenous H(2)S production in human subjects. Upon intravenous administration of Na(2)S, a rapid elevation of exhaled H(2)S concentrations was observed. The amount of exhaled H(2)S rapidly decreased after discontinuation of the infusion of Na(2)S. Exhaled H(2)S represents a detectable route of elimination after parenteral administration of Na(2)S.


Expression of three Rx homeobox genes in embryonic and adult zebrafish.
The paired-class homeobox gene, Rx, is important in eye development. In this study we analyze expression patterns of three zebrafish Rx genes (Zrx1, 2, 3) in embryos and adults. All three genes show dynamic spatiotemporal patterns of expression. Zrx3 is expressed earliest, in the anteriormost region of the neural plate, in regions that give rise to ventral diencephalon and retinae. As development proceeds, Zrx3 expression is reduced in the lateral optic primordia, and is absent in the optic cup, but is retained at the ventral midline of the diencephalon, and is expressed in hypothalamus in the adult. As the neural retina begins to differentiate, Zrx3 is re-expressed in a subset of cells in the inner nuclear layer, presumably bipolar cells, and this expression is retained in the adult. In contrast, Zrx1/2 have a slightly later onset of expression, are initially coincident with Zrx3, but then become complementary, remaining on in the optic primordia but disappearing from the ventral midline of the diencephalon. Zrx1/2 are down-regulated as the retina differentiates, except in the outer nuclear layer where they continue to be expressed at high levels in cone, but not rod, photoreceptors. This is the first transcription factor described that distinguishes between cone and rod photoreceptors.


Visuospatial attention in the rat and posterior parietal cortex lesions.
Covert attention to visuospatial stimuli was assessed in rats using a modified version of a task designed for human subjects. Rats were trained to respond toward bright target lights presented to the right or left visual space. Dim cue lights served to attract their attention prior to the onset of the bright target lights. Consistent with previous research using similar paradigms, rats in this experiment displayed longer reaction times during trials in which the cue and target lights were presented on opposite sides of visual space. Throughout pre- and post-operative testing, individual subjects showed lateralized differences in the performance of this task as indicated by asymmetries in reaction time, the percentage of correct responses, and the number of responses made to each side of visual space (response bias). Lesioning the area of cortex thought to be a possible homolog of the posterior parietal cortex in primates produced no specific effects on performance. It is suggested that this paradigm may tap into an evolutionarily conserved attentional process, but that this process may be subserved by somewhat different neural structures in different species.


Intravesical gemcitabine in combination with mitomycin C as salvage treatment in recurrent non-muscle-invasive bladder cancer.
To evaluate oncological outcomes after combination intravesical therapy with gemcitabine (GC) and mitomycin C (MMC) in the setting of recurrent non-muscle-invasive bladder cancer (NMIBC) after failure of previous intravesical therapy. We retrospectively identified patients with recurrent NMIBC after previous intravesical therapy, who refused or were not candidates for cystectomy, between 2005 and 2011. GC and MMC were sequentially instilled weekly for 6-8 weeks. Data were collected regarding patient demographics, bladder cancer history, and number and type of intravesical therapies before GC/MMC. Outcomes evaluated included time to recurrence and/or progression after GC/MMC. Recurrence-free outcomes were estimated using the Kaplan-Meier method, and Cox proportional hazards regression models were used to test the association of clinicopathological features with outcomes. In all, 27 patients were identified, 23 with high-risk disease (high-grade or carcinoma in situ) and four with intermediate-risk disease (multifocal or recurrent low-grade). All patients received prior intravesical therapy, and 17 patients (63%) received multiple courses. Twenty-four patients were treated with BCG. The median (range) disease-free survival of all patients was 15.2 (1.7-39.3) months. Seventeen patients (63%) developed recurrent bladder cancer, a median of 15.2 months after therapy. One patient progressed to muscle-invasive disease 5 months after treatment, and one developed metastatic disease 22 months after treatment. Three patients went on to cystectomy. Ten patients (37%) had no evidence of disease at last follow-up, with a median follow-up of 22.1 months. The combination of intravesical GC and MMC could offer durable recurrence-free survival to some patients with recurrent NMIBC who are not candidates for, or refuse, cystectomy.


"I Felt Better When I Moved Into My Own Place": Needs and Experiences of Intimate Partner Violence Survivors in Rapid Rehousing.
Accessing stable housing is a basic need for intimate partner violence (IPV) survivors, and rapid rehousing programs are a critical way to address homelessness. However, little is known about survivor experiences, needs, and outcomes in rapid rehousing services within IPV agencies. This study uses an exploratory approach to understand the needs and experiences of 31 survivors using vouchers facilitated by an IPV program in the U.S. Southwest. Thematic analysis of structured interviews resulted in four summary themes: getting to housing, managing multiple needs, accessing support, and facing barriers. Practice and evaluation implications are discussed.


Rosmarinic Acid as a Candidate in a Phenotypic Profiling Cardio-/Cytotoxicity Cell Model Induced by Doxorubicin.
Advances in cancer treatment have led to significant improvements in long-term survival in many types of cancer, but heart dysfunction and heart failure, associated with cancer treatment, have also increased. Anthracyclines are the main cause of this type of cardiotoxicity. In this study, we describe a combined experimental and cell morphology analysis approach for the high-throughput measurement and analysis of a cardiomyocyte cell profile, using partial least square linear discriminant analysis (PLS-LDA) as the pattern recognition algorithm. When screening a small-scale natural compound library, rosmarinic acid (RosA), as a candidate drug, showed the same cardioprotective effect as the positive control. We investigated the protective mechanism of RosA on a human cardiomyocyte cell line (AC16) and human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). We showed that RosA pretreatment suppressed doxorubicin (Dox)-induced cell apoptosis and decreased the activity of caspase-9. RosA promotes the expression of Heme oxygenase-1 (HO-1) and reduces the production of reactive oxygen species (Ros), which is induced by Dox. Meanwhile, it can also promote the expression of cardiac-development-related protein, including histone deacetylase 1 (HDAC1), GATA binding protein 4 (GATA4) and troponin I3, cardiac type (CTnI). Collectively, our data support the notion that RosA is a protective agent in hiPSC-CMs and has the potential for therapeutic use in the treatment of cancer therapy-related cardiac dysfunction and heart failure.


Integrated intervertebral device for anterior cervical fusion: An initial experience.
To analyze the clinical and radiographic results following the use of integrated intervertebral implant in patients with cervical spine degenerative disease. Though excellent results have been reported following anterior cervical discectomy and fusion using iliac crest autograft/allograft with plating, the morbidity associated with autograft harvest and small chances of complications with plating always exists. Recently, there has been development of a cervical stand-alone cage with integrated fixation for cervical fusion and stabilization with a possible low morbidity and optimal clinical outcome. A retrospective study of 16 patients who underwent anterior cervical discectomy and fusion using the integrated intervertebral device was performed. Intra-operative parameters, clinical features [Neck Disability Index (NDI), visual analog scale (VAS) score for neck/arm pain], and presence or absence of dysphagia was recorded. Radiographs were evaluated for assessment of implant failure and fusion. Mean age of patients was 54 years (range: 38-84 years) with male: female ratio of 1:3. Follow-up ranged from 6 to 12 months (mean: 10 months). In the early postoperative period, 2 of the 15 patients (13%) patients had mild dysphagia that resolved during follow-up with no patient having complaints of dysphagia at 3-month follow-up. One of the patients with diffuse idiopathic skeletal hyperostosis (DISH) and severe preoperative dysphagia had significant improvement in swallowing function at 3-month follow-up that was stable at 1-year follow-up. There was no evidence of implant failure, with fusion occurring in 95% (19/20) of operated levels. Analysis of follow-up VAS and NDI scores showed significant reduction in VAS score for neck pain (P < 0.019), radicular arm pain (P < 0.003), and NDI score (P < 0.007) in 77, 92, and 77% of patients, respectively, at a mean follow-up of 10 months (6-12 months). Our preliminary results with the use of this cervical stand-alone anterior fusion device with integrated screw fixation show its efficacy in anterior cervical decompression and fusion with stabilization with optimal clinical and radiographic outcome. Lower chances of dysphagia with no device-related complications are appealing, which needs to be verified in larger studies.


Diagnostic value of physical tests for isolated chronic acromioclavicular lesions.
Chronic acromioclavicular joint lesions are a common source of pain and disability in the shoulder. The goal of this study was to evaluate diagnostic values of physical tests for isolated, chronic acromioclavicular joint lesions. A retrospective case-control study. Between 1994 and 2002, 35 patients underwent a distal clavicle excision for isolated acromioclavicular joint lesions. The results of 3 commonly used examinations for acromioclavicular joint lesions were calculated for sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy. The cross body adduction stress test showed the greatest sensitivity (77%), followed by the acromioclavicular resisted extension test (72%) and active compression test (41%). The active compression test had the greatest specificity (95%). All tests had a negative predictive value of greater than 94%, but the positive predictive value was less than 30% for all tests. The active compression test had the highest overall accuracy (92%), followed by the acromioclavicular resisted extension test (84%) and the cross arm adduction stress test (79%). Combinations of the tests increased the diagnostic values for chronic acromioclavicular joint lesions. These tests have utility in evaluating patients with acromioclavicular joint pathologic lesions, and a combination of these physical tests is more helpful than isolated tests.


[General principles for treatment of early rheumatoid arthritis].
The main goals of the treatment of a patient with RA are: to reduce pain, joint swelling and constitutional symptoms such as fatigue, to improve joint function, stop progression of bone-cartilage damage , prevent disabilities and reduce morbidity and mortality. In recent years, the therapeutic concept of early RA (first 12 months of symptoms) has undergone major changes. Three aspects in particular have become the basis of the new treatment paradigm: early diagnosis, immediate beginning of Disease Modifying Antirheumatic Drugs therapy (DMARD) and strict control of the inflammatory activity. In this article, the authors review the general principles of management of patients with early RA.


No Casual Relationship Between T2DM and the Risk of Infectious Diseases: A Two-Sample Mendelian Randomization Study.
In epidemiological studies, it has been proven that the occurrence of type 2 diabetes mellitus (T2DM) is related to an increased risk of infectious diseases. However, it is still unclear whether the relationship is casual. We employed a two-sample Mendelian randomization (MR) to clarify the causal effect of T2DM on high-frequency infectious diseases: sepsis, skin and soft tissue infections (SSTIs), urinary tract infections (UTIs), pneumonia, and genito-urinary infection (GUI) in pregnancy. And then, we analyzed the genome-wide association study (GWAS) meta-analysis of European-descent individuals and conducted T2DM-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) that were associated with genome-wide significance (p < 5 × 10-8). MR estimates were obtained using the inverse variance-weighted (IVW), the MR-Egger regression, the simple mode (SM), weighted median, and weighted mode. The UK Biobank (UKB) cohort (n > 500,000) provided data for GWASs on infectious diseases. MR analysis showed little evidence of a causal relationship of T2DM with five mentioned infections' (sepsis, SSTI, UTI, pneumonia, and GUI in pregnancy) susceptibility [odds ratio (OR) = 0.99999, p = 0.916; OR = 0.99986, p = 0.233; OR = 0.99973, p = 0.224; OR = 0.99997, p = 0.686; OR, 1.00002, p = 0.766]. Sensitivity analysis showed similar results, indicating the robustness of causality. There were no heterogeneity and pleiotropic bias. T2DM would not be causally associated with high-frequency infectious diseases (including sepsis, SSTI, UTI, pneumonia, and GUI in pregnancy).


[Are the international changes in coronary mortality since 1968 incidental?].
Important negative and positive changes in coronary mortality have been observed since 1968 in several industrialized countries. It is extremely important to know if those changes are spurious or real. It is the aim of this paper to try to resolve the problem by comparing coronary mortality with all causes mortality and other causes of death in 29 countries in the period 1968 to 1987, in men and women. The comparison was done not only as means obtained over the years, but also as slopes estimated in each country by linear regression of mortality versus the years of observation, and finally as yearly % changes in mortality. The comparisons were done between coronary mortality of men with other causes of death from men or women: all causes, cancers from colon, rectum, prostate and breast, and finally total cardiovascular, stroke and diabetes under three different conditions: means, slopes and % changes. The overall result was that when coronary mortality changed similar changes were observed for all causes mortality and the other causes of death. The majority of the data point to saturated fat intake as the common factor in the observed changes in different types of mortality. Those findings make a spurious origin of the change in mortality very unlikely and underscore the importance of vital statistics for monitoring public health.


Isolation and characterization of an autonomously replicating sequence from Ustilago maydis.
DNA fragments that function as autonomously replicating sequences (ARSs) have been isolated from Ustilago maydis. When inserted into an integrative transforming vector, the fragments increased the frequency of U. maydis transformation several-thousandfold. ARS-containing plasmids were transmitted in U. maydis as extrachromosomal elements through replication. They were maintained at a level of about 25 copies per cell but were mitotically unstable. One ARS characterized in detail, which we called UARS1, was localized to a 1.7-kilobase fragment. UARS1 contained a cluster of active sequences. This element could be reduced further into three separate subfragments, each of which retained ARS activity. The smallest one was 383 base pairs (bp) long. Although not active itself in yeast, this small fragment contained seven 8-bp direct repeats, two contiguous 30-bp direct repeats, and five 11-bp units in both orientations with sequences similar but not identical to the consensus sequence found to be crucial for ARS activity in Saccharomyces cerevisiae.


Structural aspects of HLA class I epitopes reacting with human monoclonal antibodies in Ig-binding, C1q-binding and lymphocytotoxicity assays.
This study addresses the reactivity patterns of human cytotoxic HLA class I epitope-specific monoclonal antibodies in Ig-binding and complement component C1q-binding Luminex assays in comparison with complement-dependent lymphocytotoxicity data reported at the 13th International HLA Workshop. Some monoclonal antibodies reacted similarly with epitope-carrying alleles in all three assays but others showed different reactivity patterns. These reactivity differences were analyzed with HLAMatchmaker and we incorporated the concept that eplets are essential parts of structural epitopes which can contact the six Complementarity Determining Regions (CDRs) of antibody. The data show that technique-dependent reactivity patterns are associated with distinct differences between polymorphic amino acid configurations on eplet-defined structural epitopes. The findings have been viewed in context of antigen-antibody complex formation that results in the release of free energy necessary to stabilize binding and to induce conformational changes in the antibody molecule to expose the C1q binding site, the first step of complement activation. Moreover the amount of free energy should be sufficient to induce a conformational change of C1q thereby initiating the first stages of the classical complement cascade leading to lymphocytotoxicity. The complement-fixing properties of HLA antibodies require not only specific recognition of eplets but also depend on interactions of other CDRs with critical amino acid configurations within the structural epitope. Eplet-carrying alleles that lack such configurations may only bind with antibody. This concept is important to our understanding whether or not complement-fixing donor-specific HLA antibodies can initiate antibody-mediated rejection.


Extracorporeal membrane oxygenation for neonatal collapse caused by enterovirus myocarditis.
To describe the effect of extracorporeal membrane oxygenation (ECMO) on survival and cardiac outcome of neonates with myocardial failure secondary to severe enterovirus (EV) myocarditis. Retrospective case series. A 15-bed cardiac paediatric intensive care unit (ICU). We describe the clinical presentations, cardiac findings, ECMO characteristics and outcome of seven neonates with severe EV myocarditis. Additionally, 35 previously reported cases of EV myocarditis supported with ECMO are presented. Extracorporeal membrane oxygenation. Seven neonates presented with cardiovascular collapse within the first 10 days after birth and required ECMO support. Echocardiography showed left ventricular dysfunction in all and additional right ventricular dysfunction in four patients. ECG showing widespread ST changes as well as elevated troponin I indicated myocardial damage. All patients were cannulated onto ECMO shortly after ICU admission. None of the patients suffered cardiac arrest prior to ECMO initiation. Four patients survived ECMO and three survived to hospital discharge. All three survivors showed complete cardiac recovery after a median follow-up of 34 months. The survival rate in 35 previously reported cases was 34% (12/35) and including our seven cases 36% (15/42). In this case series, ECMO initiation prevented further deterioration and cardiac arrest in neonates with severe EV myocarditis and not responding to conventional medical therapies. Moreover, complete cardiac recovery occurred in survivors. However, these neonates may need long ECMO runs and are at increased risk for mechanical complications. Furthermore, mortality remains high due to greater disease severity.


Prevention of recurrent acute otitis media: chemoprophylaxis versus tympanostomy tubes.
Otitis media has long been recognized as one of the most common diseases of childhood. Several therapeutic modalities have been advocated for the prevention of recurrent episodes of acute otitis media (AOM). A blinded, prospective, randomized study was designed to determine the efficacy of tympanostomy tubes, antibiotic prophylaxis, and placebo. Children with recurrent AOM were entered in the study and followed for at least 6 months. A total of 65 children completed the protocol. Sixty-three of those were under the age of 4 years. Treatment failure was defined as two or more episodes of AOM or otorrhea in less than 3 months. Five of 22 children in the tympanostomy tube group failed, compared to 12 of 20 in the placebo group (p = .02). There were 8 or 21 treatment failures in the sulfisoxazole group. Children with otitis media with effusion (OME) at the time of their initial visit had significantly less middle ear disease when treated with tympanostomy tubes. Tympanostomy tube insertion for prophylaxis of recurrent acute otitis is supported by these findings. Improvement of recurrent AOM was observed in the sulfisoxazole group, but was not statistically significant.


Time-frequency changes in electromyographic signals after hamstring lengthening surgery in children with cerebral palsy.
Increased knee flexion during stance is a common gait deviation in the child with cerebral palsy (CP), with distal hamstring lengthening surgeries being an accepted course of treatment. Post-operatively, improvements in gait kinematics have been reported, however little change is noted in the patterns of muscle activity as portrayed by onset and offset timing in the surface electromyographic (sEMG) signals. Similar analysis based on the frequency content of the sEMG signals has seldom been applied, yet may provide additional insight into changes in muscle activity in response to surgery. The purpose of this study was to determine if changes in the time-frequency characteristics of the sEMG, extracted using wavelet analysis techniques, corresponded to improved gait kinematics observed post-surgical intervention, and whether there existed a relationship between frequency characteristics of the sEMG signals and the type of surgery required to correct gait kinematics. Data were collected from 16 children with typical development (TD) and 17 children with CP pre- and post-surgery. Muscle activity was recorded from the medial hamstring (MH) and vastus lateralis (VL) muscles, processed using the wavelet transform, and analyzed using functional principal component analyses (PCA). Results indicated that frequency differences were present pre-operatively depending if surgery was to be performed bilaterally or involved bone modification. Post-operatively, frequency characteristics of the VL more closely approximated those observed in children with TD, agreeing with the improved gait kinematics. MH characteristics, however, for the surgical groups demonstrated a deviation away for TD reflecting the altered muscle structure.


Regulation of crayfish, Orconectes virilis, tail muscle lactate dehydrogenase (LDH) in response to anoxic conditions is associated with alterations in phosphorylation patterns.
Lactate dehydrogenase (LDH), the terminal enzyme of anaerobic glycolysis, has a crucial role in sustaining ATP production by glycolysis during periods of anoxia via regenerating NAD+ through the production of lactate. The present study examined the effects of prolonged (20h) anoxic submergence on LDH from the tail muscle of an anoxia-tolerant crayfish (Orconectes virilis). LDH was purified to homogeneity from tail muscle of both aerobic control and anoxic crayfish in a three step process. Analysis of the kinetic parameters and the stability of LDH showed that the Vmax in the pyruvate-reducing direction was significantly higher for the enzyme from anoxic crayfish whereas in the lactate-oxidizing direction the Vmax was significantly higher for the control enzyme. Differential scanning fluorimetry was used to assess thermal unfolding of crayfish LDH. The results showed that the enzyme from control muscle had a significantly higher melting temperature (greater thermal stability) than the anoxic enzyme form, suggesting that there was a structural difference between the two enzyme forms. Immunoblotting of purified LDH implicated post-translational modification as the reason for this difference; purified LDH from aerobic control crayfish showed significantly higher amounts of serine/threonine phosphorylation than did the anoxic enzyme form. This study provides evidence for anoxia-induced modifications of crayfish muscle LDH that may contribute significantly to modulating enzyme function under anoxic conditions.


Development of a miniaturized heart-lung machine for neonates with congenital heart defect.
Predominantly, standard adult heart lung machines are used for pediatric cardiac surgery, only with individually downsized components. Downsizing is limited, e.g., by the required gas exchange surface. To diminish complications, we developed a new miniaturized heart lung machine (MiniHLM) for neonates, with significantly reduced priming volume and blood contact surface by integration of all major system components in one single device. In particular, a rotary blood pump is centrically integrated into the oxygenator and the cardiotomy reservoir with integrated heat exchanger is directly connected. Thus, tubing is only necessary between patient and MiniHLM. A total priming volume of 102 ml could be achieved for the entire extracorporeal circuit (including arterial/venous line), in contrast to the currently smallest device on the market with 213 ml. In first animal experiments with female New Zealand rabbits, the MiniHLM guaranteed both a sufficient gas exchange and an adequate blood flow; 12 rabbits could successfully be weaned off after 1 hour of aortic clamp time. The first in vitro and in vivo tests confirm the concept of the MiniHLM. Its low priming volume and blood contact surface may significantly reduce complications during heart surgery in neonates.


Potentiation of the photodynamic action of hypericin.
Hypericin (HY) is an interesting photosensitizer with dark activity and photodynamic therapy (PDT) effects via p53-independent pathway. In photodynamic diagnosis (PDD) of bladder cancer using HY, very high sensitivity and specificity were reported, in comparison with its counterpart, 5-aminolevulinic acid (5-ALA). HY was tested for the detection of human gastric cancer. It was also studied for treating some cancers and age-related macular degeneration and showed some promising findings. Several strategies to enhance the efficacy of HY-PDD and HY-PDT are reviewed. Using fractionated light dosing, fractionated drug dosing, hyperthermia, adjuvants such as oxygen carrier/antiangiogenesis, chemical modifications, and formulation approaches to enhance the PDT effects of HY are topics of this review. Despite cutting-edge technology approach such as preparing transferring-mediated targeting HY liposomes and nanoparticles of HY, such preparations did not always offer the desired enhanced treatment effects. It turns out that simple solutions of HY, especially those prepared without using plasma protein, were more successful in enhancing the delivery of HY for in vitro and in vivo systems. Thus, the HY-PDT with these formulations performed better. It is anticipated that HY-PDD and HY-PDT can be enhanced and optimized with the right combination of light dosimetry and drug dose in an effective formulation containing a suitable adjuvant. Hyperoxygenation and hyperthermia can also be used to further enhance the efficacy of HY-PDT.


Evolution of host range in Coleosporium ipomoeae, a plant pathogen with multiple hosts.
Plants and their pathogens coevolve locally. Previous investigations of one host-one pathogen systems have demonstrated that natural selection favors pathogen genotypes that are virulent on a broad range of host genotypes. In the present study, we examine a system consisting of one pathogen species that infects three host species in the morning glory genus Ipomoea. We show that many pathogen genotypes can infect two or three of the host species when tested on plants from nonlocal communities. By contrast, pathogen genotypes are highly host-specific, infecting only one host species, when tested on host species from the local community. This pattern indicates that within-community evolution narrows the host breadth of pathogen genotypes. Possible evolutionary mechanisms include direct selection for narrow host breadth due to costs of virulence and evolution of ipomoea resistance in the host species.


Harsh parenting in relation to child emotion regulation and aggression.
This study presents a model of harsh parenting that has an indirect effect, as well as a direct effect, on child aggression in the school environment through the mediating process of child emotion regulation. Tested on a sample of 325 Chinese children and their parents, the model showed adequate goodness of fit. Also investigated were interaction effects between parents' and children's gender. Mothers' harsh parenting affected child emotion regulation more strongly than fathers', whereas harsh parenting emanating from fathers had a stronger effect on child aggression. Fathers' harsh parenting also affected sons more than daughters, whereas there was no gender differential effect with mothers' harsh parenting. These results are discussed with an emphasis on negative emotionality as a potentially common cause of family perturbations, including parenting and child adjustment problems.


Isolation and partial characterization of a new reovirus in the Chinese mitten crab, Eriocheir sinensis H Milne Edwards.
A second type of freshwater crab reovirus has been isolated from Chinese mitten crab, Eriocheir sinensis H. Milne Edwards, in China; we named it E. sinensis reovirus (EsRV816). The negatively stained virion is a non-enveloped icosahedral particle, 60 ± 5 nm in diameter. Its genome is composed of 10 dsRNA linear pieces exhibiting an electrophoretic pattern of 5/3/2. The largest segment (RNA-1) was cloned and sequenced. The deduced amino acid sequence, corresponding to the RdRp of the virus, showed 26% identity with the RdRp of Operophtera brumata (L.) cypovirus 19 in the genus Cypovirus and 24% identity with RdRp of Nilaparvata lugens (Stal) reovirus in the genus Fijivirus. On the basis of its ultrastructure and physicochemical properties, this virus is quite different from other crab reoviruses, and particularly with another freshwater crab reovirus EsRV905, recently classified in a new genus Cardoreovirus. This virus (EsRV816) possesses all the characters of the members of the reoviridae family and could represent a new genus.


Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations.
Phase variation occurs in many pathogenic and commensal bacteria and is a major generator of genetic variability. A putative advantage of phase variation is to counter reductions in variability imposed by nonselective bottlenecks during transmission. Genomes of Campylobacter jejuni, a widespread food-borne pathogen, contain multiple phase-variable loci whose rapid, stochastic variation is generated by hypermutable simple sequence repeat tracts. These loci can occupy a vast number of combinatorial expression states (phasotypes) enabling populations to rapidly access phenotypic diversity. The imposition of nonselective bottlenecks can perturb the relative frequencies of phasotypes, changing both within-population diversity and divergence from the initial population. Using both in vitro testing of C. jejuni populations and a simple stochastic simulation of phasotype change, we observed that single-cell bottlenecks produce output populations of low diversity but with bimodal patterns of either high or low divergence. Conversely, large bottlenecks allow divergence only by accumulation of diversity, while interpolation between these extremes is observed in intermediary bottlenecks. These patterns are sensitive to the genetic diversity of initial populations but stable over a range of mutation rates and number of loci. The qualitative similarities of experimental and in silico modeling indicate that the observed patterns are robust and applicable to other systems where localized hypermutation is a defining feature. We conclude that while phase variation will maintain bacterial population diversity in the face of intermediate bottlenecks, narrow transmission-associated bottlenecks could produce host-to-host variation in bacterial phenotypes and hence stochastic variation in colonization and disease outcomes.IMPORTANCE Transmission and within-host spread of pathogenic organisms are associated with selective and nonselective bottlenecks that significantly reduced population diversity. In several bacterial pathogens, hypermutable mechanisms have evolved that mediate high-frequency reversible switching of specific phenotypes, such as surface structures, and hence counteract bottleneck-associated reductions in population diversity. Here, we investigated how combinations of hypermutable simple sequence repeats interact with nonselective bottlenecks by using a stochastic computer model and experimental data for Campylobacter jejuni, a food-borne pathogen. We find that bottleneck size qualitatively alters the output populations, with large bottlenecks maintaining population diversity while small bottlenecks produce dramatic shifts in the prevalence of particular variants. We conclude that narrow bottlenecks are capable of producing host-to-host variation in repeat-controlled bacterial phenotypes, leading to a potential for stochastic person-to-person variations in disease outcome for C. jejuni and other organisms with similar hypermutable mechanisms.


Twist promotes angiogenesis in pancreatic cancer by targeting miR-497/VEGFA axis.
Angiogenesis is a critical step in the growth and dissemination of malignant diseases, including pancreatic cancer. Twist has been shown to stimulate angiogenesis in the tumor site. However, whether Twist contributes to angiogenesis in pancreatic cancer remains unknown. In this paper, we found that the expression of Twist was significantly increased in human pancreatic cancer cell lines and pancreatic cancer specimens. It is also closely engaged to adverse clinical feature, diminished survival and angiogenesis in pancreatic cancer patients. The up-regulation of Twist was found to be promoting cell growth, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs) in vitro. By contrast, the silencing of Twist inhibited orthotopic xenograft tumor growth, metastasis and angiogenesis. Subsequent investigations disclosed that Twist was regulated by miR-497 directly, leading to the increased level of Vascular Endothelial Growth Factor-A (VEGFA). Moreover, gain-of-function and loss-of-function studies demonstrated that miR-497 could suppress the pro-proliferative, angiogenic and metastatic ability of pancreatic cancer cells. The ectopic expression of VEGFA obviously abrogated the anti-angiogenic effect induced by Twist knockdown, whereas the silencing of VEGFA markedly rescued the pro-angiogenic effect of Twist. By analyzing the expression levels of miR-497, Twist was found inversely correlated with miR-497 in pancreatic cancer tissues, and a positive correlation was found between Twist and VEGFA levels in pancreatic cancer specimens. In conclusion, our results suggested that the Twist/miR-497/VEGFA axis is significantly correlated with metastasis and angiogenesis in pancreatic cancer.


Prevalence of Sjögren's syndrome in a closed rural community.
To define the prevalence of Sjögren's syndrome (SS) through an epidemiological survey in a closed rural community. The classification of SS is based on the validated criteria reported by a multicentre study performed in Europe and supported by the Epidemiology Committee of the European Community (EEC-COMAC Epidemiology). The population under study consisted of 837 women aged 18 years or older, residing in the Astakos community of Aitoloakarnania, Greece. The study protocol was subdivided in two parts. In part I, an exhaustive epidemiological survey of these women was conducted in July and August of 1992. The validated questionnaire used in the survey assesses both ocular and oral involvement. In part II, 45 of the women reporting symptoms of both dry eye and dry mouth were approached for a full examination based on the validated set of classification criteria of SS. The full complement of the diagnostic tests was performed on 35 of these women. A subject is classified as a definite primary SS case if at least four of six items of the subject's test items are positive. If three of six items are positive the subject is classified as a probable primary SS case. The classification criteria for definite primary SS were satisfied by five women. This number corresponds to an estimated prevalence of 0.60% (exact 95% CI 0.19%, 1.39%). Probable primary SS was diagnosed for 25 women (prevalence = 2.99%). Because of the loss of follow up (10 of 45) and the use of slightly stricter criteria for inclusion of possible SS cases in part II of the study, we consider our estimate of the prevalence of SS to be conservative. This study concurring with other recent reports, suggests that SS is more prevalent than previously thought.


2022 EULAR points to consider for remote care in rheumatic and musculoskeletal diseases.
Remote care and telehealth have the potential to expand healthcare access, and the COVID-19 pandemic has called for alternative solutions to conventional face-to-face follow-up and monitoring. However, guidance is needed on the integration of telehealth into clinical care of people with rheumatic and musculoskeletal diseases (RMD). To develop EULAR points to consider (PtC) for the development, prioritisation and implementation of telehealth for people with RMD. A multidisciplinary EULAR task force (TF) of 30 members from 14 European countries was established, and the EULAR standardised operating procedures for development of PtC were followed. A systematic literature review was conducted to support the TF in formulating the PtC. The level of agreement among the TF was established by anonymous online voting. Four overarching principles and nine PtC were formulated. The use of telehealth should be tailored to patient's needs and preferences. The healthcare team should have adequate equipment and training and have telecommunication skills. Telehealth can be used in screening for RMD as preassessment in the referral process, for disease monitoring and regulation of medication dosages and in some non-pharmacological interventions. People with RMD should be offered training in using telehealth, and barriers should be resolved whenever possible.The level of agreement to each statement ranged from 8.5 to 9.8/10. The PtC have identified areas where telehealth could improve quality of care and increase healthcare access. Knowing about drivers and barriers of telehealth is a prerequisite to successfully establish remote care approaches in rheumatologic clinical practice.


All gifts large and small: toward an understanding of the ethics of pharmaceutical industry gift-giving.
Much attention has been focused in recent years on the ethical acceptability of physicians receiving gifts from drug companies. Professional guidelines recognize industry gifts as a conflict of interest and establish thresholds prohibiting the exchange of large gifts while expressly allowing for the exchange of small gifts such as pens, note pads, and coffee. Considerable evidence from the social sciences suggests that gifts of negligible value can influence the behavior of the recipient in ways the recipient does not always realize. Policies and guidelines that rely on arbitrary value limits for gift-giving or receipt should be reevaluated.


Relation between occupational asthma case history, bronchial methacholine challenge, and specific challenge test in patients with suspected occupational asthma.
Inhalative methacholine challenge (MC) was performed in 229 subjects presumed to suffer from occupational asthma due to exposure to airborne latex allergens (n = 62), flour (n = 28), isocyanates (n = 114), or irritants in hairdressers' salons (n = 25). They were also subjected to specific challenges with the occupational agents they were exposed to, completed a questionnaire using an abbreviated version of the ATS-DLD, and were interviewed by an experienced physician. Bronchial hyperresponsiveness in MC was defined by the results obtained in a previous study with 81 healthy volunteers. The threshold in these controls was set at a cumulative MC dose of 0.3 mg, corresponding to a sensitivity of 95%. The main purpose of the study was to investigate whether the MC and/or the occupational asthma case history are reliable predictors of the specific challenge test outcomes. In 40-72% of examined subjects, workplace-related asthma complaints occurred, with bronchial hyperreactivity in the MC ranging from 48% to 61%. However, only 12-25% demonstrated a significant bronchoconstructive reaction in the specific challenge test. MC results are only moderately associated with workplace-related asthma case histories. Positive outcomes of challenges with occupational agents are well correlated with positive MC results plus occupational asthma case histories. The combination of MC and occupational asthma case history shows a relatively high specificity (62%, 86%, 80%), but the sensitivity was moderately low (83%, 71%, 52%). MC sensitivities were 92%, 71%, and 62% (case histories of hairdressers were not available). We conclude that in most cases, occupational asthma (as defined by a specific challenge test response) is combined with bronchial hyperresponsiveness and workplace-related asthmatic symptoms. However, subjects of each exposure group demonstrated bronchial hyperresponsiveness and complained of workplace-related asthmatic symptoms, but occupational asthma could not be proved in the specific challenge test. In subjects with a positive occupational asthma case history, a negative MC test result can almost rule out a positive specific challenges test result. Hence, the MC test can reduce performance of the laborious specific challenge test.


Toward an automated workflow for the study of plasma protein-drug interactions based on capillary electrophoresis-frontal analysis combined with in-capillary mixing of interacting partners.
Capillary electrophoresis-frontal analysis (CE-FA) together with mobility shift affinity CE is the most frequently used mode of affinity CE for a study of plasma protein-drug interactions, which is a substantial part of the early stage of drug discovery. Whereas in the classic CE-FA setup the sample is prepared by off-line mixing of the interaction partners in the sample vial outside the CE instrument and after a short incubation period loaded into the capillary and analysed, in this work a new methodological approach has been developed that combines CE-FA with the mixing of interacting partners directly inside the capillary. This combination gives rise to a fully automated and versatile methodology for the characterization of these binding interactions besides a substantial reduction in the amounts of sample compounds used. The minimization of possible experimental errors due to the full involving of sophisticated CE instrument in the injection procedure, mixing and separation instead of manual manipulation is another fundamental benefit. The in-capillary mixing is based on the transverse diffusion of laminar flow profile methodology introduced by Krylov et al. using its multi-zone injection modification presented by Řemínek at al.. Actually, after the method optimization, the alternate introduction of six plugs of drug and six plugs of bovine serum protein in BGE, each injected for 3 s at a pressure of -10 mbar (-1 kPa) into the capillary filled by BGE, was found to be the best injection procedure. The method repeatability calculated as RSDs of plateau highs of bovine serum albumin and propranolol as model sample compounds were better than 3.44 %. Its applicability was finally demonstrated on the determination of apparent binding parameters of bovine serum albumin for basic drugs propranolol and lidocaine and acid drug phenylbutazone. The values obtained by a new on-line CE-FA methodology are in agreement with values estimated by classic off-line CE-FA, as well as with literature data obtained using different techniques.


Variation in the FcgammaR3B gene among distinct Brazilian populations.
The FCGR3B gene codes for the FcgammaR3b receptor, which occurs in three polymorphic forms representing the human neutrophil antigens (HNA)-1a, HNA-1b, and HNA-1c. The alleles that code for these antigens are FCGR3B*1, FCGR3B*2, and FCGR3B*3, respectively. New variants of these alleles have been recently described. In order to study the frequency of these alleles and the occurrence of variant forms, we sequenced part of the FCGR3B gene in 149 individuals belonging to four distinct Brazilian populations, i.e., 60 Amerindians, 30 Whites of European descent, 30 Afro-Brazilians, and 30 Japanese. The FCGR3B*1 allele showed high frequency among Amerindians (0.850), with the value detected representing the highest frequency described thus far for this allele in population studies. Its frequency was 0.660 in the Japanese population studied, a value equal to that observed in Afro-Brazilians (0.600) and higher than that observed in Whites (0.480). The FCGR3B*3 allele was only found among Afro-Brazilians, where it occurred at a frequency of 0.080, which was lower than the frequency observed among Afro-North Americans (0.207) and Ugandans (0.166). Two variant haplotypes were detected among Amerindians and Afro-Brazilians, occurring in six individuals (four Amerindians and two Afro-Brazilians). The variant haplotype FCGR3B*1 A227G, which occurred in homozygosis in two Amerindians and in heterozygosis in two Afro-Brazilians, is described for the first time in the present report. In general, these data reveal variability in the frequency of alleles of the FCGR3B gene compared to other populations of the same genetic background in other regions of the world.


[Control of lysogeny and a genetic map of the temperate phage SM of Pseudomonas aeruginosa].
76 mutants with impaired ability to lysogenize host cells were isolated in SM phage after mutagenesis using several chemical mutagens. By means of complementation test, these mutants were distributed into two groups, cI and cII. The mutants of the cI group were similar phenotypically to the cI mutants of phage lambda defective in synthesis of repressor. The mutants of the cII group establish and support the lysogenic state in infected cells with very low frequency. Temperature-sensitive mutants belonging to 13 complementation groups and nonlysogenizing mutants of the cI and cII groups were used in genetic mapping of SM phage. Mutual positions of markers and relative distances between them were determined by the method of two-factorial crosses. The greatest distance equal to 20 units of recombination was determined between ts 88 marker and one of early genes marked with ts 105 mutation. The genes cI and cII are closely linked to each other and also to ts 105 marker and are situated at one end of the genetic map.


An observational study of complications in chickenpox with special reference to unusual complications in an apex infectious disease hospital, Kolkata, India.
Chickenpox can cause serious complications and even death in persons without any risk factors. To observe the different complications with special reference to unusual complications of chickenpox and their outcomes. The present study was a prospective observational study where 300 patients suffering from chickenpox were evaluated with special reference to unusual complications and outcomes. The usual complications of chickenpox commonly observed were acute hepatitis in 30 (10%) and cerebellar ataxia in 22 patients (7.3%), whereas common unusual complications were acute pancreatitis in 45 (15%), hemorrhagic rash in 10 (3.3%), Guillain-Barrι syndrome in 4 (1.3%), disseminated intravascular coagulation in 4 (1.3%), necrotizing fasciitis in 4 (1.3%), and acute renal failure in 3 patients (1%). It had been observed that most of these unusual complications occurred in patients without any risk factor. A total of 18 patients (6%) died in this study and of them 12 patients (4%) died due to unusual complications. Compulsory childhood varicella vaccination including vaccination of risk groups and susceptible individuals are all essential to reduce the incidence of chickenpox, associated complications, and subsequent death.


[Application of a device for evacuation of fragments of biological tissue and uroliths in endoscopic operations].
The proposed evacuator allows prevention of regurgitation of fragments of resected tissue of destructed bladder stones from the lower cavity of the device to the upper one, and then to the urinary bladder and, thus, it reduces loss of the biological material fragment for morphological investigation as well as the bladder stones fragments for an analysis of their chemical composition and structure, more effectively and quicklywash off the urinary bladder during endoscopic operations.


Connexin40 nonsense mutation in familial atrial fibrillation.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with substantial morbidity and mortality. Genetic variants play important roles in the pathogenesis of AF. However, AF is a genetically heterogeneous disorder, and the genetic determinants in most patients with AF remain to be identified. In this study, the entire coding region of the connexin40 gene, encoding the cardiac gap junction membrane channel protein alpha5, was sequenced in 126 unrelated probands with familial AF. A novel heterozygous mutation, c.145C<T, in connexin40, was identified in a proband. The mutation was predicted to introduce a premature stop codon at amino acid position 49 (p.Q49X). This nonsense mutation was present in all the living relatives of the mutation carrier, co-segregating with AF in the family with a penetrance of 100%. However, it was absent in 200 ethnically matched unrelated control individuals. The findings suggest a pathogenic link between the compromised connexin40 function and familial AF, hence providing new insight into the molecular mechanisms involved in AF.


Analysis of host-pathogen modulators of autophagy during Mycobacterium Tuberculosis infection and therapeutic repercussions.
Mycobacterium tuberculosis is one of the most deadly human pathogens known today in modern world, responsible for about 1.5 million deaths annually. Development of TB disease occurs only in 1 out of 10 individuals exposed to the pathogen which indicates that the competent host defense mechanisms exist in majority of the hosts to control the infection. In the last decade, autophagy has emerged as a key host immune defense mechanism against intracellular M. tuberculosis infection. Autophagy has been demonstrated not only as an effective antimicrobial mechanism for the clearance of M. tuberculosis, but the process has also been suggested to prevent excessive inflammation to avoid the adverse effects of infection on host. Nevertheless, increasing evidences also show that in order to enhance its intracellular survival, M. tuberculosis has also evolved multiple strategies to compromise the optimal functioning of host autophagic machinery. This review describes an overview of the various host signaling pathways such as pattern recognition receptors, cytokines, nutrient starvation and other cellular stress that have been implicated in induction of autophagy during M. tuberculosis infection. The review also chalk out the complex interplay of several bacterial factors of M. tuberculosis that are known to be involved in compromising autophagy mediated defense of the host. A comprehensive understanding of the interaction of bacterial and host factors at the intersections of autophagic pathways could provide integrative insights for the development of autophagy-based prophylactics and novel therapeutic interventions for TB.


Divergent strabismus fixus--a case report.
Strabismus fixus is a rare condition and usually is of convergent type in which one or both eyes are anchored in a position of extreme adduction. Convergent type strabismus fixus is considered to be a congenital disorder and a part of congenital extraocular muscle fibrosis syndrome. Villasecca and Martinez described an acquired type of strabismus fixus. Hayashi et al reported that progressive esotropia could develop into the acquired type of convergent strabismus fixus. There are very few reports of divergent strabismus fixus in the literature. It may or may not be accompanied by ptosis or generalized extraocular muscle fibrosis. In our report, a case of divergent type strabismus fixus is described and discussed.


[Balneotherapy, health care and public health].
The actual interest of Spa-therapy in public health is considered as a way of improving health, well-being state or as prevention or treatment of different diseases. The various definitions of health are exposed and its possible influence in human beings, and in particular the complexity of the Spa-therapy. The possible positive effects of the Spa-therapy have been tested in the official Centers of several countries and have been considered of great value in Health Education its signification as a primary, secondary and tertiary health agent.


Efficacy and safety of diphenylcyclopropenone alone or in combination with anthralin in the treatment of chronic extensive alopecia areata: a retrospective case series.
Some patients with chronic extensive alopecia areata (AA) may be refractory to topical immunotherapy. Combination therapy is recommended for such patients. Efficacy and safety of a combination therapy with diphenylcyclopropenone (DPCP) and anthralin in chronic extensive AA is unknown. We sought to determine whether the combination therapy of DPCP and anthralin is superior to DPCP alone in chronic extensive AA. We retrospectively analyzed the efficacy, side effects, and relapse rates of DPCP (alone or with anthralin) in chronic extensive AA. A total of 47 patients (22 were treated only with DPCP, and 25 with DPCP and anthralin for at least 30 weeks) were evaluated. Complete hair regrowth was observed in 36.4% and 72% of the patients who received DPCP and combination therapy, respectively (P = .01). Hair regrowth duration was shorter with combination therapy (P = .01). Regrowth rates of the eyebrows, eyelashes, and beard in patients on combination therapy were higher than those in patients on DPCP (P = .01). Side effects such as folliculitis, hyperpigmentation, and staining of skin, hair, and clothes were more common in combination therapy group. The retrospective design and small number of patients are limitations. Combination therapy with DPCP and anthralin is superior to DPCP alone in chronic extensive AA.


Cortical organization of inhibition-related functions and modulation by psychopathology.
Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology.


Multivariate Analysis of Genotype-Phenotype Association.
With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map has important consequences for gene identification and may shed light on the evolvability of organisms.


PLGA-PEG Nanoparticles Facilitate In Vivo Anti-Alzheimer's Effects of Fucoxanthin, a Marine Carotenoid Derived from Edible Brown Algae.
The marine natural product fucoxanthin has been reported previously to produce anti-Alzheimer's disease (AD) neuroprotective effects in vitro and in vivo. Fucoxanthin was also demonstrated to be safe in preclinical and small population clinical studies, but the low bioavailability of fucoxanthin in the central nervous system (CNS) has limited its clinical applications. To overcome this, poly lactic-co-glycolic acid-block-polyethylene glycol loaded fucoxanthin (PLGA-PEG-Fuc) nanoparticles with diameter at around 200 nm and negative charge were synthesized and suggested to penetrate into the CNS. Loaded fucoxanthin could be liberated from PLGA-PEG nanoparticles by sustained released in the physiological environment. PLGA-PEG-Fuc nanoparticles were shown to significantly inhibit the formation of Aβ fibrils and oligomers. Moreover, these nanoparticles were taken up by both neurons and microglia, leading to the reduction of Aβ oligomers-induced neurotoxicity in vitro. Most importantly, intravenous injection of PLGA-PEG-Fuc nanoparticles prevented cognitive impairments in Aβ oligomers-induced AD mice with greater efficacy than free fucoxanthin, possibly via acting on Nrf2 and NF-κB signaling pathways. These results altogether suggest that PLGA-PEG nanoparticles can enhance the bioavailability of fucoxanthin and potentiate its efficacy for the treatment of AD, thus potentially enabling its future use for AD therapy.


Murine fibromodulin: cDNA and genomic structure, and age-related expression and distribution in the knee joint.
The genomic structure of murine fibromodulin was determined, and its age-related expression and distribution were characterized in knee epiphyses, with decorin studied for reference. Fibromodulin, as well as decorin, have roles in collagen fibrillogenesis both in vitro and in vivo. The murine fibromodulin gene, Fmod, was similar with that in other species, with three exons and 86% of the translated sequence in exon 2. The 2.7 kb long cDNA contains an open reading frame of 1131 nt. Fibromodulin mRNA levels were highest in tissues rich in fibrillar collagens type I or type II. During growth, the distribution of fibromodulin mRNA was similar with that of type II collagen, with the highest levels between 5 days and 1 month of age. Thereafter, the expression of type II collagen declined to a level near the detection limit, whereas the fibromodulin expression decreased less markedly to a level of approx. 35% of maximum, and remained constant throughout the rest of the observation period. In contrast, decorin mRNA levels were the highest in old animals. Pericellular deposition of fibromodulin was strong around the late-hypertrophic chondrocytes of the secondary ossification centre and in the growth plate. In young epiphyses, both fibromodulin and decorin were found interterritorially, mainly in the uncalcified and deep-calcified cartilage. In the old mice, calcified cartilage became enriched with regard to fibromodulin, while, in contrast, decorin deposition diminished, particularly near the tidemark. In the subchondral bone trabeculae, decorin was found in the endosteum of growing, but not in the mature, epiphyses. Differences in the expression and distribution profiles suggest different roles for fibromodulin and decorin in the regulation of collagen fibrillogenesis, maintenance of the fibril organization and matrix mineralization. As fibromodulin is deposited closer to cells than decorin, it may have a primary role in collagen fibrillogenesis, whereas decorin might be involved in the maintenance of fibril structures in the interterritorial matrix.


A cloud computing based platform for sleep behavior and chronic diseases collaborative research.
The objective of this study is to propose a Cloud Computing based platform for sleep behavior and chronic disease collaborative research. The platform consists of two main components: (1) a sensing bed sheet with textile sensors to automatically record patient's sleep behaviors and vital signs, and (2) a service-oriented cloud computing architecture (SOCCA) that provides a data repository and allows for sharing and analysis of collected data. Also, we describe our systematic approach to implementing the SOCCA. We believe that the new cloud-based platform can provide nurse and other health professional researchers located in differing geographic locations with a cost effective, flexible, secure and privacy-preserved research environment.